Methods and devices for passive residual lung volume reduction and functional lung volume expansion

ABSTRACT

The volume of a hyperinflated lung compartment is reduced by sealing a distal end of the catheter in an airway feeding the lung compartment. Air passes out of the lung compartment through a passage in the catheter while the patient exhales. A one-way flow element associated with the catheter prevents air from re-entering the lung compartment as the patient inhales. Over time, the pressure of regions surrounding the lung compartment cause it to collapse as the volume of air diminishes. Residual volume reduction effectively results in functional lung volume expansion. Optionally, the lung compartment may be sealed in order to permanently prevent air from re-entering the lung compartment.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.15/358,483 (Attorney Docket No. 20920-720.302), filed which is acontinuation of U.S. patent application Ser. No. 13/938,025 (AttorneyDocket No. 20920-720.301), filed Jul. 9, 2013, now U.S. Pat. No.9,533,116, which is a continuation of U.S. patent application Ser. No.12/820,547 (Attorney Docket No. 20920-720.503), filed Jun. 22, 2010, nowU.S. Pat. No. 8,496,006, which is a continuation-in-part of U.S. patentapplication Ser. No. 11/685,008 (Attorney Docket No. 20920-720-501),filed Mar. 12, 2007; U.S. patent application Ser. No. 12/820,547, isalso a continuation-in-part of U.S. patent application Ser. No.11/296,951 (Attorney Docket No. 20920-714.501,), filed Dec. 7, 2005, nowU.S. Pat. No. 7,883,471, which claims the benefit and priority of U.S.Provisional Patent Application Nos.: 60/645,711 (Attorney Docket20920-714.101), filed Jan. 20, 2005; 60/696,940 (Attorney Docket20920-714.102), filed Jul. 5, 2005; and 60/699,289 (Attorney Docket20920-715.101), filed Jul. 13, 2005. The full disclosures of all theabove-referenced patent applications are hereby incorporated herein byreference.

BACKGROUND OF THE INVENTION Field of the Invention

The present invention relates generally to medical methods andapparatus. More particularly, the present invention relates to methodsand apparatus for endobronchial residual lung volume reduction bypassive deflation of hyperinflated segments with functional lung volumeexpansion as a result.

Chronic obstructive pulmonary disease is a significant medical problemaffecting 16 million people or about 6% of the U.S. population. Specificdiseases in this group include chronic bronchitis, asthmatic bronchitis,and emphysema. While a number of therapeutic interventions are used andhave been proposed, none is completely effective, and chronicobstructive pulmonary disease remains the fourth most common cause ofdeath in the United States. Thus, improved and alternative treatmentsand therapies would be of significant benefit.

Of particular interest to the present invention, lung function inpatients suffering from some forms of chronic obstructive pulmonarydisease can be improved by reducing the effective lung volume, typicallyby resecting diseased portions of the lung. Resection of diseasedportions of the lungs both promotes expansion of the non-diseasedregions of the lung and decreases the portion of inhaled air that goesinto the lungs but is unable to transfer oxygen to the blood. Lungvolume reduction is conventionally performed in open chest orthoracoscopic procedures where the lung is resected, typically usingstapling devices having integral cutting blades.

While effective in many cases, conventional lung volume reductionsurgery is significantly traumatic to the patient, even whenthoracoscopic procedures are employed. Such procedures often result inthe unintentional removal of healthy lung tissue and frequently leaveperforations or other discontinuities in the lung, which result in airleakage from the remaining lung. Even technically successful procedurescan cause respiratory failure, pneumonia, and death. In addition, manyolder or compromised patients are not able to be candidates for theseprocedures.

As an improvement over open surgical and minimally invasive lung volumereduction procedures, endobronchial lung volume reduction procedureshave been proposed. For example, U.S. Pat. Nos. 6,258,100 and 6,679,264describe placement of one-way valve structures in the airways leading todiseased lung regions. It is expected that the valve structures willallow air to be expelled from the diseased region of the lung whileblocking reinflation of the diseased region. Thus, over time, the volumeof the diseased region will be reduced and the patient condition willimprove.

While promising, the use of implantable, one-way valve structures isproblematic in at least several respects. The valves must be implantedprior to assessing whether they are functioning properly. Thus, if thevalve fails to either allow expiratory flow from or inhibit inspiratoryflow into the diseased region, that failure will only be determinedafter the valve structure has been implanted, requiring surgicalremoval. Additionally, even if the valve structure functions properly,many patients have diseased lung segments with collateral flow fromadjacent, healthy lung segments. In those patients, the lung volumereduction of the diseased region will be significantly impaired, evenafter successfully occluding inspiration through the main airway leadingto the diseased region, since air will enter collaterally from theadjacent healthy lung region. When implanting one-way valve structures,the existence of such collateral flow will only be evident after thelung region fails to deflate over time, requiring further treatment.

For these reasons, it would be desirable to provide improved andalternative methods and apparatus for effecting residual lung volumereduction in hyperinflated and other diseased lung regions. The methodsand apparatus will preferably allow for passive deflation of an isolatedlung region without the need to implant a one-way valve structure in thelung. The methods and apparatus will preferably be compatible with knownprotocols for occluding diseased lung segments and regions afterdeflation, such as placement of plugs and occluding members within theairways leading to such diseased segments and regions. Additionally,such methods and devices should be compatible with protocols foridentifying and treating patients having diseased lung segments andregions which suffer from collateral flow with adjacent healthy lungregions. At least some of these objectives will be met by the inventionsdescribed hereinbelow.

2. Description of the Background Art

Methods for performing minimally invasive and endobronchial lung volumereduction are described in the following patents and publications: U.S.Pat. Nos. 5,972,026; 6,083,255; 6,258,100; 6,287,290; 6,398,775;6,527,761; 6,585,639; 6,679,264; 6,709,401; 6,878,141; 6,997,918;2001/0051899; and 2004/0016435.

BRIEF SUMMARY OF THE INVENTION

The present invention provides methods and apparatus for passivelyreducing the residual volume (the volume of air remaining after maximalexhalation) of a hyperinflated or otherwise diseased lung compartment orsegment. By “passively reducing,” it is meant that air can be removedfrom the diseased lung region without the use of a vacuum aspiration todraw the air from the region. Typically, such passive reduction willrely on a non-implanted one-way flow structure, which permits air to beexhaled or exhausted from the lung region while preventing or inhibitingthe inspiration of air back into the lung region. Thus, the methods ofthe present invention will not require the permanent implantation ofvalves or other structures prior to actually achieving the desiredresidual lung volume reduction, as with the one-way implantable valvestructures of the prior art.

The methods and apparatus of the present invention can be terminated andall apparatus removed should it appear for any reason that the desiredresidual lung volume reduction is not being achieved. Commonly, suchfailure can be the result of collateral flow into the diseased lungregion from adjacent healthy lung region(s). In such cases, steps can betaken to limit or stop the collateral flow and allow resumption of thepassive lung volume reduction protocols. In other cases, it might bedesirable or necessary to employ open surgical, thoracoscopic, or othersurgical procedures for lung resection.

Patients who successfully achieve residual volume reduction ofhyperinflated or other diseased lung regions in accordance with theprinciples of the present invention will typically have those regionssealed permanently to prevent reinflation. Such sealing can be achievedby a variety of known techniques, including the application ofradiofrequency or other energy for shrinking or sealing the walls of theairways feeding the lung region. Alternatively, synthetic or biologicalglues could be used for achieving sealing of the airway walls. Mostcommonly, however, expandable plugs will be implanted in the airwaysleading to the deflated lung region to achieve the sealing.

In a first aspect of the present invention, methods for reducing theresidual volume of a hyperinflated lung compartment comprise sealinglyengaging a distal end of a catheter in an airway feeding the lungcompartment. Air is allowed to be expelled from the lung compartmentthrough a passage in the catheter while the patient is exhaling, and airis blocked from re-entering the lung compartment through the catheterpassage while the patient is inhaling. As the residual volumediminishes, the hyperinflated lung compartment reduces in size freeingup the previously occupied space in the thoracic cavity. Consequently, agreater fraction of the Total Lung Capacity (TLC), which is thevolumetric space contained in the thoracic cavity that is occupied bylung tissue after a full inhalation, becomes available for the healthierlung compartments to expand, and the volume of the lung available forgas exchange commonly referred to in clinical practice as the lung'sFunctional Vital Capacity (FVC) or Vital Capacity (VC) increases, theresult of which is effectively a functional lung volume expansion.

The hyperinflated lung compartment will usually be substantially free ofcollateral flow from adjacent lung compartments, and optionally thepatient can be tested for the presence of such collateral flow, forexample using techniques taught in copending, commonly assignedapplication Ser. Nos. 11/296,951 (Attorney Docket No.: 017534-002820US),filed on Dec. 7, 2005; 11/550,660 (Attorney Docket No. 017534-003020US),filed on Oct. 18, 2006; and application Ser. No. 11/428,762 (AttorneyDocket No. 017534-003010US), filed on Jul. 5, 2006, the full disclosuresof which are incorporated herein by reference.

Alternatively, the methods of the present invention for reducingresidual lung volume can be performed in patients having collateral flowchannels leading into the hyperinflated or other diseased lungcompartment. In such cases, the collateral flow channels may first beblocked, for example, by introducing glues, occlusive particles,hydrogels or other blocking substances, as taught for example incopending application Ser. No. 11/684,950 (Attorney Docket No.017534-004000US), filed on Mar. 12, 2007, the full disclosure of whichis incorporated herein by reference. In other cases, where the flowchannels are relatively small, those channels will partially or fullycollapse as the residual lung volume is reduced. In such cases, thepatient may be treated as if the collateral flow channels did not exist.The effectiveness of reduction in hyperinflation, however, will dependon the collateral resistance between the hyperinflated compartment andthe neighboring compartments, as illustrated in FIG. 7, where residualvolume reduction is negligible when the resistance to collateral flowR_(coll) is very small (significant collateral flow channels) andmaximally effective when R_(.sub.) coll is very high (no collateral flowchannels).

In all of the above methods, it may be desirable to introduce anoxygen-rich gas into the lung compartment while or after the lung volumeis reduced in order to induce or promote absorption atelectasis.Absorption atelectasis promotes absorption of the remaining or residualgas in the compartment into the blood to further reduce the volume,either before or after permanent sealing of the lung volume compartmentor segment.

In a second aspect, the present invention provides catheters forisolating and deflating hyperinflated and other diseased lungcompartments. The catheter comprises a catheter body, an expandableoccluding member on the catheter body, and a one-way flow elementassociated with the catheter body. The catheter body usually has adistal end, a proximal end, and at least one lumen extending from alocation at or near the distal end to a location at or near the proximalend. At least a distal portion of the catheter body is adapted to beadvanced into and through the airways of a lung so that the distal endcan reach an airway that feeds a target lung compartment or segment tobe treated. The expandable occluding member is disposed near the distalend of the catheter body and is adapted to be expanded in the airwaythat feeds the target lung compartment or segment so that saidcompartment or segment can be isolated, with access provided onlythrough the lumen or catheter body when the occluding member isexpanded. The one-way flow element is adapted to be disposed within orin-line with the lumen of the catheter body in order to allow flow in adistal-to-proximal direction so that air will be expelled from theisolated lung compartment or segment as the patient exhales. The one-wayflow element, however, inhibits or prevents flow through the lumen in aproximal-to-distal direction so that air cannot enter the isolated lungcompartment or segment while the patient is inhaling.

For the intended endobronchial deployment, the catheter body willtypically have a length in the range from 20 cm to 200 cm, preferablyfrom 80 cm to 120 cm, and a diameter near the distal end in the rangefrom 0.1 mm to 10 mm, preferably from 1 mm to 5 mm. The expandableoccluding member will typically be an inflatable balloon or cuff, wherethe balloon or cuff has a width in the range from 1 mm to 30 mm,preferably from 5 mm to 20 mm, when inflated. The one-way flow elementis typically a conventional one-way flow valve, such as a duck-billvalve, a flap valve, or the like, which is disposed in the lumen of thecatheter body, either near the distal end or at any other point withinthe lumen. Alternatively, the one-way flow element could be provided asa separate component, for example provided in a hub which is detachablymounted at the proximal end of the catheter body. In other instances, itmight be desirable to provide two or more one-way flow elements inseries within the lumen or otherwise provided in-line with the lumen inorder to enhance sealing in the inspiratory direction through the lumen.

In a third aspect of the present invention, a method for determiningwhether collateral ventilation of a hyperinflated lung compartment ispresent may involve: sealing a distal end of a catheter in an airwayfeeding the lung compartment; allowing air to be expelled from the lungcompartment through a passage in the catheter while the patient isexhaling; blocking air from entering the lung compartment through thecatheter passage while the patient is inhaling; comparing an image ofthe lung compartment with an earlier image of the lung compartmentacquired before the sealing step; and determining whether collateralventilation is present in the lung compartment, based on comparing theimage and the earlier image. In one embodiment, the compared images areCT scans, although in other embodiments alternative imaging modalitiesmay be used, such as MRI, conventional radiographs and/or the like.Typically, though not necessarily, the before and after images will becompared based on size, with a smaller size after catheter placementindicating a lack of significant collateral ventilation and little or nochange in size indicating likely significant collateral ventilation.

Optionally, one embodiment may involve advancing the catheter through abronchoscope to position the catheter distal end in the airway beforesealing. In one such embodiment, the method may also involve: detachinga hub from a proximal end of the catheter; removing the bronchoscopefrom the airway by sliding it proximally over the catheter, thus leavingthe catheter in the airway; and acquiring the image of the lungcompartment. The catheter may be left in the airway for any suitableamount of time before acquiring the image—for example in one embodimentbetween about five minutes and about twenty-four hours. In someembodiments, where it is determined that there is minimal or nosignificant collateral ventilation of the lung compartment, the methodmay further include treating the airway to permanently limit airflowinto the lung compartment.

These and other aspects and embodiments are described in further detailbelow, with reference to the attached drawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of an isolation and deflation catheterconstructed in accordance with the principles of the present invention.

FIGS. 2-4 illustrate alternative placements of one-way flow elementswithin a central lumen of the catheter of FIG. 1.

FIG. 5 illustrates the trans-tracheal endobronchial placement of thecatheter of FIG. 1 in an airway leading to a diseased lung region inaccordance with the principles of the present invention.

FIGS. 6A-6D illustrate use of the catheter as placed in FIG. 5 forisolating and reduction of the volume of the diseased lung region inaccordance with the principles of the present invention.

FIG. 7 is a graph showing the relationship between collateral resistanceR_(coll) and residual volume reduction in an isolated lung compartment.

FIGS. 8A-8D illustrate an embodiment of a minimally invasive method inwhich a catheter is advanced to the feeding bronchus of a targetcompartment.

FIGS. 9A-9D and FIG. 10 illustrate embodiments of a catheter connectedwith an accumulator.

FIGS. 11A-11B depict a graphical representation of a simplifiedcollateral system of a target lung compartment.

FIGS. 12A-12C illustrate measurements taken from the system of FIGS.11A-11B.

FIGS. 13A-13C illustrate a circuit model representing the system ofFIGS. 11A-11B.

FIGS. 14A-14B illustrate measurements taken from the system of FIGS.11A-11B.

FIGS. 15A-15D illustrate graphical comparisons yielded from thecomputational model of the collateral system illustrated in FIGS.11A-11B and FIGS. 13A-13B.

FIG. 16A illustrates a two-compartment model which is used to generate amethod quantifying the degree of collateral ventilation.

FIG. 16B illustrates an electrical circuit analog model.

FIGS. 16C-16E illustrate the resulting time changes in volumes,pressures and gas concentrations in the target compartment and the restof the lobe.

DETAILED DESCRIPTION OF THE INVENTION

Referring to FIG. 1, an endobronchial lung volume reduction catheter 10constructed in accordance with the principles of the present inventionincludes an elongate catheter body 12 having a distal end 14, a proximalend 16, and an expandable occluding member 15, such as an inflatableballoon, mounted near the distal end 14. Catheter body 12 also includesat least one lumen or central passage 18 extending generally from thedistal end 14 to the proximal end 16. Lumen 18 has a distal opening 19at or near the distal end 14 in order to permit air or other lung gasesto enter the lumen 18 and flow in a distal-to-proximal direction outthrough the proximal end of the lumen 18. Optionally, a hub 20 will beprovided at the proximal end 16, but the hub 20 is not a necessarycomponent of the catheter 10.

The catheter 10 is equipped to seal the area between the catheter body12 and the bronchial wall such that only the lumen 18 is communicatingwith the airways distal to the seal. The seal, or isolation, isaccomplished by the use of the occluding member 15, such as aninflatable member, attached to (or near) the distal tip 14 of thecatheter 10. When there is an absence of collateral channels connectingthe targeted isolated compartment to the rest of the lung, the isolatedcompartment will unsuccessfully attempt to draw air from the catheterlumen 18 during inspiration of normal respiration of the patient. Hence,during exhalation no air is returned to the catheter lumen. In thepresence of collateral channels, an additional amount of air isavailable to the isolated compartment during the inspiratory phase ofeach breath, namely the air traveling from the neighboringcompartment(s) through the collateral channels, which enables volumetricexpansion of the isolated compartment during inspiration, resultingduring expiration in air movement away from the isolated compartment toatmosphere through the catheter lumen and the collateral channels. If itis desired to perform Endobronchial Volume Reduction (EVR) on a lungcompartment, the lung compartment may be analyzed for collateralventilation prior to treatment to determine the likelihood of success ofsuch treatment. Further, if undesired levels of collateral ventilationare measured, the collateral ventilation may be reduced to a desiredlevel prior to treatment to ensure success of such treatment.

The present invention relies on placement of a one-way flow elementwithin or in-line with the lumen 18 so that flow from an isolated lungcompartment or segment (as described hereinbelow) may occur in adistal-to-proximal direction but flow back into the lung compartment orsegment is inhibited or blocked in the proximal-to-distal direction. Asshown in FIG. 2, in one embodiment a one-way flow element 22 may beprovided in the lumen 18 near the distal end 14 of the catheter body 12,immediately proximal of the distal opening 19. In an alternativeembodiment, as in FIG. 3, the same one-way flow element 22 may beprovided in the lumen 18 more proximally (either still near the distalend 14 or even more proximally in some embodiments). As shown in FIGS. 2and 3, the one-way flow element 22 may be a duck-bill valve, which opensas shown in broken line as the patient exhales to increase the pressureon the upstream or distal side of the valve 22. As the patient inhales,the pressure on the upstream or distal side of the valve is reduced,drawing the valve leaflets closed as shown in solid line.

Alternatively or additionally, the one-way flow element 22 could beprovided anywhere else in the lumen 18, and two, three, four, or moresuch valve structures could be included in order to provide redundancy.In some embodiments where the one-way flow element 22 (or elements) islocated within the lumen 18 of the catheter body 12, the hub 20 may beremovable, or alternatively the catheter 10 may not include a hub. Aswill be explained further below, this may facilitate leaving thecatheter 10 in a patient for diagnostic and/or treatment purposes. Forexample, if the catheter 10 is advanced into a patient through abronchoscope, the hub 20 may be detached to allow the bronchoscope to beremoved proximally over the catheter 10, thus leaving the catheter body12 with the one-way flow element 22 in the patient.

As a third option, a one-way valve structure 26 in the form of a flapvalve could be provided within the hub 20. The hub 20 could be removableor permanently fixed to the catheter body 12. Other structures forproviding in-line flow control could also be utilized.

In some embodiments, the catheter 10 may be coupled with a one-wayvalve, a flow-measuring device or/and a pressure sensor, all of whichare external to the body of the patient and are placed in series so asto communicate with the catheter's inside lumen 18. The one-way valveprevents air from entering the target lung compartment from atmospherebut allows free air movement from the target lung compartment toatmosphere. The flow measuring device, the pressure sensor device andthe one-way valve can be placed anywhere along the length of thecatheter lumen 18. The seal provided by the catheter 10 results, duringexpiration, in air movement away from the isolated lung compartment toatmosphere through the catheter lumen 18 and the collateral channels.Thus, air is expelled through the catheter lumen 18 during eachexhalation and will register as positive airflow on the flow-measuringdevice. Depending on the system dynamics, some air may be expelledthrough the catheter lumen 18 during exhalation in the absence ofcollateral channels, however at a different rate, volume and trend thanthat in the presence of collateral channels.

Use of the endobronchial lung volume reduction catheter 10 to reduce theresidual volume of a diseased region DR of a lung L is illustratedbeginning in FIG. 5. Catheter 10 is introduced through the patient'smouth, down past the trachea T and into a lung L. The distal end 14 ofthe catheter 10 is advanced to the main airway AW leading into thediseased region DR of the lung. Introduction and guidance of thecatheter 10 may be achieved in conventional manners, such as describedin commonly-owned U.S. Pat. Nos. 6,287,290; 6,398,775; and 6,527,761,the full disclosures of which are incorporated herein by reference. Insome embodiments, the catheter may be introduced through a flexiblebronchoscope (not shown in FIG. 5).

Referring now to FIGS. 6A-6D, functioning of the one-way valve elementin achieving the desired lung volume reduction will be described. Afterthe distal end 14 of the catheter 10 is advanced to the feeding airwayAW, the expandable occluding element 15 is expanded to occlude theairway. The expandable occluding element may be a balloon, cuff, or abraided balloon as described in copending applications Ser. Nos.60/823,734 (Attorney Docket No. 017534-003800US), filed on Aug. 28,2006, and 60/828,496 (Attorney Docket No. 017534-003900US) filed on Oct.6, 2006, the full disclosures of which are incorporated herein byreference. At that point, the only path between the atmosphere and thediseased region DR of the lung is through the lumen 18 of the catheter10. As the patient exhales, as shown in FIG. 6A, air from the diseasedregion DR flows outwardly through the lumen 18 and the one-way valveelement 22, causing a reduction in residual air within the region and aconsequent reduction in volume. Air from the remainder of the lung alsopasses outward in the annular region around the catheter 10 in a normalmanner.

As shown in FIG. 6B, in contrast, when the patient inhales, no airenters the diseased regions DR of the lung L (as long as there are nosignificant collateral passageways), while the remainder of the lung isventilated through the region around the catheter. As the patientcontinues to inhale and exhale, the air in the diseased region DR isincrementally exhausted, further reducing the lung volume as theexternal pressure from the surrounding regions of the lung is increasedrelative to the pressure within the diseased region.

As shown in FIG. 6C, after some time, typically seconds to minutes, airflow from the isolated lung segment will stop and a maximum ornear-maximum level of residual lung volume reduction within the diseasedregion DR will have been achieved. At that time, treating the patientmay comprise occluding the airway AW feeding the diseased region DR, byapplying heat, radiofrequency energy, glues, or preferably by implantingan occluding element 30, as shown in FIG. 6D. Implantation of theoccluding element may be achieved by any of the techniques described incommonly-owned U.S. Pat. Nos. 6,287,290; and 6,527,761, the fulldisclosures of which have been previously incorporated herein byreference. In some embodiments, before more permanently occluding theairway, treating the patient may comprise aspirating the target lungcompartment. When accessing a lung compartment through an occlusalstent, volume reduction therapy may be performed by aspirating throughthe catheter and stent. The catheter is then removed and the volumereduction maintained.

As described in greater detail in U.S. patent application Ser. No.11/296,951, from which the present application claims priority and whichhas been previously incorporated by reference, a catheter 10 asdescribed herein may also be used to determine whether collateralventilation is present in a lung. The '951 application describes anumber of methods and devices for use in determining such collateralventilation. Additionally or alternatively to those methods/devices, inone embodiment a catheter 10 (as described above) may be advancedthrough a bronchoscope and deployed as described in relation to FIGS. 5and 6A-6D of the present application. In this embodiment, the catheter10 includes at least one one-way flow element 22 within the lumen 18 ofthe catheter body 12. The hub 20 of the catheter 10 may then bedetached, and the bronchoscope may be removed proximally over thecatheter body 12, leaving the catheter body 12 in place in the patient.After a desired amount of time (anywhere from several minutes totwenty-four hours or more), an imaging study such as a CT scan may betaken of the patient's lung to see if the residual volume of thediseased lung compartment has decreased. Typically, this CT scan orother imaging study will be compared to a similar study taken beforeplacement of the catheter 10 to determine if placement of the catheterhas caused a reduction in residual volume in the lung compartment. If areduction is noted, this may indicate that collateral ventilation isabsent or minimal. This type of assessment may be used to help decidewhether to treat a lung compartment further, such as with an implantablevalve or blocking element.

In an alternative embodiment, the hub 20 of the catheter 10 may be lefton, and the catheter 10 and bronchoscope may be left in the patient fora short time while an imaging study is performed.

While the above is a complete description of the preferred embodimentsof the invention, various alternatives, modifications, and equivalentsmay be used. Therefore, the above description should not be taken aslimiting the scope of the invention which is defined by the appendedclaims.

Minimally invasive methods, systems and devices are provided forqualitatively and quantitatively assessing collateral ventilation in thelungs. FIGS. 8A-8D illustrate an embodiment of a minimally invasivemethod in which a catheter 10 is advanced through a tracheobronchialtree to the feeding bronchus B of the target area CT the compartmenttargeted for treatment or isolation. The catheter 10 comprises a shaft12 having at least one lumen therethrough and an occlusion member 15mounted near its distal end. The catheter 10 is equipped to seal thearea between the catheter shaft 12 and the bronchial wall such that onlya lumen inside the catheter which extends the entire length of thecatheter is communicating with the airways distal to the seal. The seal,or isolation, is accomplished by the use of the occlusion member 15,such as an inflatable member, attached to the distal tip of the catheter10.

On the opposite end of the catheter 10, external to the body of thepatient, a one-way valve 16, a flow-measuring device 48 or/and apressure sensor 40 are placed in series so as to communicate with thecatheter's inside lumen. The one-way valve 16 prevents air from enteringthe target compartment C_(s) from atmosphere but allows free airmovement from the target compartment C_(s) to atmosphere. When there isan absence of collateral channels connecting the targeted isolatedcompartment C_(s) to the rest of the lung, as illustrated in FIGS.8A-8B, the isolated compartment C_(s) will unsuccessfully attempt todraw air from the catheter lumen during inspiration of normalrespiration of the patient. Hence, during exhalation no air is returnedto the catheter lumen. In the presence of collateral channels, asillustrated in FIGS. 8C-8D, an additional amount of air is available tothe isolated compartment C_(s) during the inspiratory phase of eachbreath, namely the air traveling from the neighboring compartment(s) Cthrough the collateral channels CH, which enables volumetric expansionof the isolated compartment C_(s) during inspiration, resulting duringexpiration in air movement away from the isolated compartment C_(s) toatmosphere through the catheter lumen and the collateral channels CH.Thus, air is expelled through the catheter lumen during each exhalationand will register as positive airflow on the flow-measuring device 48.This positive airflow through the catheter lumen provides an indicationof whether or not there is collateral ventilation occurring in thetargeted compartment C_(s).

This technique of measuring collateral flow in a lung compartment isanalogous to adding another lung compartment, or lobe with infinitelylarge compliance, to the person's lungs, the added compartment beingadded externally. Depending on the system dynamics, some air may beexpelled through the catheter lumen during exhalation in the absence ofcollateral channels, however at a different rate, volume and trend thanthat in the presence of collateral channels.

In other embodiments, the catheter 10 is connected with an accumulatoror special container 42 as illustrated in FIGS. 9A-9D, 6. The container42 has a very low resistance to airflow, such as but not limited to e.g.a very compliant bag or slack collection bag. The container 42 isconnected to the external end or distal end 14 of the catheter 10 andits internal lumen extending therethrough in a manner in which theinside of the special container 42 is communicating only with theinternal lumen. During respiration, when collateral channels are notpresent as illustrated in FIGS. 9A-9B, the special container 42 does notexpand. The target compartment Cs is sealed by the isolation balloon 14so that air enters and exits the non-target compartment C. Duringrespiration, in the presence of collateral channels as illustrated inFIGS. 9C-9D, the special container 42 will initially increase in volumebecause during the first exhalation some portion of the airflow receivedby the sealed compartment C_(s) via the collateral channels CH will beexhaled through the catheter lumen into the external special container42. The properties of the special container 42 are selected in order forthe special container 42 to minimally influence the dynamics of thecollateral channels CH, in particular a highly inelastic specialcontainer 42 so that it does not resist inflation. Under the assumptionthat the resistance to collateral ventilation is smaller duringinspiration than during expiration, the volume in the special container42 will continue to increase during each subsequent respiratory cyclebecause the volume of air traveling via collateral channels CH to thesealed compartment C_(s) will be greater during inspiration than duringexpiration, resulting in an additional volume of air being forcedthrough the catheter lumen into the special container 42 duringexhalation.

Optionally, a flow-measuring device 48 or/and a pressure sensor 40 maybe included, as illustrated in FIG. 10. The flow-measuring device 48and/or the pressure sensor 40 may be disposed at any location along thecatheter shaft 12 (as indicated by arrows) so as to communicate with thecatheter's internal lumen. When used together, the flow-measuring device48 and the pressure sensor 40 may be placed in series. A one-way valve16 may also be placed in series with the flow-measuring device 48 or/andpressure sensor 40. It may be appreciated that the flow-measuring device48 can be placed instead of the special container 42 or between thespecial container 42 and the isolated lung compartment, typically at butnot limited to the catheter-special container junction, to measure theair flow rate in and out of the special container and hence byintegration of the flow rate provide a measure of the volume of airflowing through the catheter lumen from/to the sealed compartment C_(s).

It can be appreciated that measuring flow can take a variety of forms,such as but not limited to measuring flow directly with theflow-measuring device 48, and/or indirectly by measuring pressure withthe pressure sensor 40, and can be measured anywhere along the cathetershaft 12 with or without a one-way valve 16 in conjunction with the flowsensor 48 and with or without an external special container 42.

Furthermore, a constant bias flow rate can be introduced into the sealedcompartment C_(s) with amplitude significantly lower than the flow rateexpected to be measured due to collateral flow via the separate lumen inthe catheter 10. For example, if collateral flow measured at the flowmeter 48 is expected to be in the range of 1 ml/min, the bias flow ratecan be, but not limited to one tenth (0.1) or one one-hundredth (0.01)of that amount of equal or opposite amplitude. The purpose of the biasflow is to continuously detect for interruptions in the detectioncircuit (i.e., the working channel of the bronchoscope and any othertubing between the flow meter and catheter) such as kinks or clogs, andalso to increase response time in the circuit (due to e.g. inertia).Still, a quick flush of gas at a high flow rate (which is distinguishedfrom the collateral ventilation measurement flow rate) can periodicallybe introduced to assure an unclogged line.

In addition to determining the presence of collateral ventilation of atarget lung compartment, the degree of collateral ventilation may bequantified by methods of the present invention. In one embodiment, thedegree of collateral ventilation is quantified based on the resistancethrough the collateral system R_(coll). R_(coll) can be determined basedon the following equation:

$\begin{matrix}{{\frac{\overset{\_}{P_{b}}}{\overset{\_}{Q_{fm}}}} = {R_{coll} + R_{saw}}} & (1)\end{matrix}$

where R_(coll) constitutes the resistance of the collateral channels,R_(saw) characterizes the resistance of the small airways, and P_(b) andQ_(fm) represent the mean pressure and the mean flow measured by acatheter isolating a target lung compartment in a manner similar to thedepictions of FIGS. 8A-8D.

For the sake of simplicity, and as a means to carry out a proof ofprinciple, FIGS. 11A-11B depict a graphical representation of asimplified collateral system of a target lung compartment C_(s). Asingle elastic compartment 31 represents the target lung compartmentC_(s) and is securely positioned inside a chamber 32 to prevent anypassage of air between the compartment 31 and the chamber 32. Thechamber 32 can be pressurized to a varying negative pressure relative toatmosphere, representing the intrathoracic pressure P_(p1). The elasticcompartment 31, which represents the target compartment in the lungC_(s) communicates with the atmospheric environment through passageway88. In addition, the elastic compartment 31 also communicates with theatmospheric environment through collateral pathway 41, representingcollateral channels CH of the target compartment of the lung C_(s).

A catheter 34 is advanceable through the passageway 88, as illustratedin FIGS. 11A-11B. The catheter 34 comprises a shaft 36, an inner lumen37 therethrough and an occlusion member 38 mounted near its distal end.The catheter 34 is specially equipped to seal the area between thecatheter shaft 36 and the passageway 88 such that only the lumen 37inside the catheter 34, which extends the length of the catheter 34,allows for direct communication between the compartment 31 andatmosphere. On the opposite end of the catheter 34, a flow-measuringdevice 42 and a pressure sensor 40 are placed in series to detectpressure and flow in the catheter's inside lumen 37. A one-way valve 16positioned next to the flow measuring device 42 allows for the passageof air in only one direction, namely from the compartment 31 toatmosphere. The flow measuring device 42, the pressure sensor device 40and the one-way valve 16 can be placed anywhere along the length of thecatheter lumen, typically at but not limited to the proximal end of thecatheter shaft 36. It should be appreciated that measuring pressureinside the compartment 31 can be accomplished in a variety of forms,such as but not limited to connecting the pressure sensor 40 to thecatheter's inside lumen 37. For instance, it can also be accomplished byconnecting the pressure sensor 40 to a separate lumen inside thecatheter 34, which extends the entire length of the catheter 34communication with the airways distal to the seal.

At any given time, the compartment 31 may only communicate to atmosphereeither via the catheter's inside lumen 37 representing R_(saw) and/orthe collateral pathway 41 representing R_(coll). Accordingly, duringinspiration, as illustrated in FIG. 11A, P_(p1) becomes increasinglynegative and air must enter the compartment 31 solely via collateralchannels 41. Whereas during expiration, illustrated in FIG. 11B, air mayleave via collateral channels 41 and via the catheter's inside lumen 37.

FIGS. 12A-12C illustrate measurements taken from the system of FIGS.11A-11B during inspiration and expiration phases. FIG. 12A illustrates acollateral flow curve 50 reflecting the flow Q_(coll) through thecollateral pathway 41. FIG. 12B illustrates a catheter flow curve 52reflecting the flow Q_(fm) through the flow-measuring device 42. Duringinspiration, air flows through the collateral pathway 41 only; no airflows through the flow-measuring device 42 since the one-way valve 16prevents such flow. Thus, FIG. 12A illustrates a negative collateralflow curve 50 and FIG. 12B illustrates a flat, zero-valued catheter flowcurve 52. During expiration, a smaller amount of air, as compared to theamount of air entering the target compartment C_(s) during inspiration,flows back to atmosphere through the collateral pathway 41, asillustrated by the positive collateral flow curve 50 of FIG. 12A, whilethe remaining amount of air flows through the catheter lumen 37 back toatmosphere, as illustrated by the positive catheter flow curve 52 ofFIG. 12B.

The volume of air flowing during inspiration and expiration can bequantified by the areas under the flow curves 50, 52. The total volumeof air V₀ entering the target compartment 31 via collateral channels 41during inspiration can be represented by the colored area under thecollateral flow curve 50 of FIG. 12A. The total volume of air V₀ may bedenoted as V₀=V₁+V₂, whereby V₁ is equal to the volume of air expelledvia the collateral channels 41 during expiration (indicated by thegrey-colored area under the collateral flow curve 50 labeled V₃), and V₂is equal to the volume of air expelled via the catheter's inside lumen37 during expiration (indicated by the colored area under the catheterflow curve 52 of FIG. 12B labeled V₄).

The following rigorous mathematical derivation demonstrates the validityof these statements and the relation stated in Eq. 1:

Conservation of mass states that in the short-term steady state, thevolume of air entering the target compartment 31 during inspiration mustequal the volume of air leaving the same target compartment 31 duringexpiration, hence

V ₀=−(V ₃ +V ₄)  (2)

Furthermore, the mean rate of air entering and leaving the targetcompartment solely via collateral channels during a complete respiratorycycle (T_(resp)) can be determined as

$\begin{matrix}{\overset{\_}{Q_{coll}} = {\frac{V_{0} + V_{3}}{T_{resp}} = \frac{V_{2}}{T_{resp}}}} & (3)\end{matrix}$

where V₂ over T_(resp) represents the net flow rate of air entering thetarget compartment 31 via the collateral channels 41 and returning toatmosphere through a different pathway during T_(rep). Accordingly, V₂accounts for a fraction of V₀, the total volume of air entering thetarget compartment 31 via collateral channels 41 during T_(resp), henceV₀ can be equally defined in terms of V₁ and V₂ as

V ₀ =V ₁ +V ₂  (4)

where V₁ represents the amount of air entering the target compartment 31via the collateral channels 41 and returning to atmosphere through thesame pathway. Consequently, substitution of V₀ from Eq. 4 into Eq. 3yields

V ₁ =V ₂  (5)

and substitution of V₀ from Eq. 2 into the left side of Eq. 4 followingsubstitution of V₁ from Eq. 5 into the right side of Eq. 4 results in

−V ₄ =V ₂  (6)

Furthermore, the mean flow rate of air measured at the flowmeter 42during T_(resp) can be represented as

$\begin{matrix}{\overset{\_}{Q_{fm}} = \frac{V_{4}}{T_{resp}}} & (7)\end{matrix}$

where substitution of V₄ from Eq. 6 into Eq. 7 yields

$\begin{matrix}{\overset{\_}{Q_{fm}} = {{- \frac{V_{2}}{T_{resp}}} = {- \overset{\_}{Q_{coll}}}}} & (8)\end{matrix}$

Ohms's law states that in the steady state

$\begin{matrix}{\mspace{20mu} {{\overset{\_}{P_{s}} = {\overset{\_}{Q_{coil}} \cdot R_{\text{?}}}}{\text{?}\text{indicates text missing or illegible when filed}}}} & (9)\end{matrix}$

where P_(s) represents the mean inflation pressure in the targetcompartment required to sustain the continuous passage of Q_(coll)through the resistive collateral channels represented by R_(coll).Visual inspection of the flow and pressure signals (FIG. 12C) within asingle T_(resp) shows that during the inspiratory time, P_(b)corresponds to P_(s) since no air can enter or leave the isolatedcompartment 31 via the catheter's inside lumen 37 during the inspiratoryphase. During expiration, however, P_(b)=0 since it is measured at thevalve opening where pressure is atmospheric, while P_(s) must stillovercome the resistive pressure losses produced by the passage of Q_(fm)through the long catheter's inside lumen 37 represented by R_(saw)during the expiratory phase effectively making P_(s) less negative thanP_(b) by Q_(fm) .R_(saw). Accordingly

$\begin{matrix}{\overset{\_}{P_{s}} = {\overset{\_}{P_{b}} + {\overset{\_}{Q_{fm}} \cdot R_{saw}}}} & (10)\end{matrix}$

and substitution of P_(s) from Eq. 9 into Eq. 10 results in

$\begin{matrix}{\overset{\_}{P_{b}} = {{\overset{\_}{Q_{coll}} \cdot R_{coll}} - {\overset{\_}{Q_{fm}} \cdot R_{saw}}}} & (11)\end{matrix}$

after subsequently solving for P_(b) . Furthermore, substitution ofQ_(coll) from Eq. 8 into Eq. 11 yields

$\begin{matrix}{\overset{\_}{P_{b}} = {{- \overset{\_}{Q_{fm}}} \cdot \left( {R_{coll} + R_{saw}} \right)}} & (12)\end{matrix}$

and division of Eq. 12 by Q_(fm) finally results in

$\begin{matrix}{\frac{\overset{\_}{P_{b}}}{\overset{\_}{Q_{fm}}} = {- \left( {R_{coll} + R_{saw}} \right)}} & (13)\end{matrix}$

where the absolute value of Eq. 13 leads back to the aforementionedrelation originally stated in Eq. 1.

The system illustrated in FIGS. 11A-11B can be represented by a simplecircuit model as illustrated in FIGS. 13A-13C. The air storage capacityof the alveoli confined to the isolated compartment 31 representingC_(s) is designated as a capacitance element 60. The pressure gradient(P_(s)-P_(b)) from the alveoli to atmosphere via the catheter's insidelumen 37 is caused by the small airways resistance, R_(saw), and isrepresented by resistor 64. The pressure gradient from the alveoli toatmosphere through the collateral channels is generated by theresistance to collateral flow, R_(coll), and is represented by resistor62.

Accordingly, the elasticity of the isolated compartment 31 isresponsible for the volume of air obtainable solely across R_(coll)during the inspiratory effort and subsequently delivered back toatmosphere through R_(saw) and R_(coll) during expiration. Pressurechanges during respiration are induced by the variable pressure source,P_(pt) representing the varying negative pleural pressure within thethoracic cavity during the respiratory cycle. An ideal diode 66represents the one-way valve 16, which closes during inspiration andopens during expiration. Consequently, as shown in FIGS. 14A-14B, theflow measured by the flow meter (Q_(fm)) is positive during expirationand zero during inspiration, whereas the pressure recorded on thepressure sensor (P_(b)) is negative during inspiration and zero duringexpiration.

Evaluation of Eqs. 1 & 8 by implementation of a computational model ofthe collateral system illustrated in FIGS. 11A-11B and FIGS. 13A-13Cyields the graphical comparisons presented in FIGS. 15A-15D. FIG. 15Adisplays the absolute values of mean Q_(fm)(|Q_(fm) |) and meanQ_(coll)(|Q_(coll) |) while the FIG. 15B shows the model parametersR_(coll)+R_(saw) plotted together with |P_(b) /Q_(coll) | as a functionof R_(coll). The values denote independent realizations ofcomputer-generated data produced with different values of R_(coll) whileR_(saw) is kept constant at 1 cmH₂O/(ml/s). FIG. 15A displays theabsolute values of |Q_(fm) | and |Q_(coll) | while FIG. 15C shows themodel parameters R_(coll)+R_(saw) plotted together with |P_(b) /Q_(coll)| as a function of R_(saw). The values denote independent realizationsof computer-generated data produced with different values of R_(saw)while R_(coll) is kept constant at 1 cmH₂O/(ml/s). It becomes quiteapparent from FIGS. 15A-15B that the flow is maximal whenR_(coll)≈R_(saw) and diminishes to zero as R_(coll) approaches thelimits of either “overt collaterals” or “no collaterals”. Accordingly,small measured flow Q_(fm) can mean both, very small and very largecollateral channels and hence no clear-cut decision can be maderegarding the existence of collateral ventilation unlessR_(coll)+R_(saw) is determined as |P_(b) /Q_(fm) |. The reason for thisis that when R_(coll) is very small compared to R_(saw), all gas volumeentering the target compartment via the collateral channels leaves viathe same pathway and very little gas volume is left to travel toatmosphere via the small airways as the isolated compartment empties.The measured pressure P_(b), however, changes accordingly andeffectively normalizes the flow measurement resulting in an accuraterepresentation of R_(coll)+R_(saw), which is uniquely associated withthe size of the collateral channels and the correct degree of collateralventilation.

Similarly, FIGS. 15C-15D supplement FIGS. 15A-15B as it shows how themeasured flow Q_(fm) continuously diminishes to zero as R_(saw) becomesincreasingly greater than R_(coll) and furthermore increases to amaximum, as R_(saw) turns negligible when compared to R_(coll). WhenR_(saw) is very small compared to R_(coll) practically all gas volumeentering the target compartment via the collateral channels travels backto atmosphere through the small airways and very little gas volume isleft to return to atmosphere via the collateral channels as the isolatedcompartment empties. Thus, determination of |P_(b) /Q_(fm) | results inan accurate representation of R_(coll)+R_(saw) regardless of theunderlying relation amongst R_(coll) and R_(saw). In a healthy human,resistance through collateral communications, hence R_(coll), supplyinga sublobar portion of the lung is many times (10-100 times) as great asthe resistance through the airways supplying that portion, R_(saw)(Inners 1979, Smith 1979, Hantos 1997, Suki 2000). Thus in the normalindividual, R_(coll) far exceeds R_(saw) and little tendency forcollateral flow is expected. In disease, however, this may not be thecase (Hogg 1969, Terry 1978). In emphysema, R_(saw) could exceedR_(coll) causing air to flow preferentially through collateral pathways.

Therefore, the above described models and mathematical relationships canbe used to provide a method which indicates the degree of collateralventilation of the target lung compartment of a patient, such asgenerating an assessment of low, medium or high degree of collateralventilation or a determination of collateral ventilation above or belowa clinical threshold. In some embodiments, the method also quantifiesthe degree of collateral ventilation, such generating a value whichrepresents R_(coll). Such a resistance value indicates the geometricsize of the collateral channels in total for the lung compartment. Basedon Poiseuille's Law with the assumption of laminar flow,

R∝(η×L)/r ⁴  (14)

wherein η represents the viscosity of air, L represents the length ofthe collateral channels and r represents the radius of the collateralchannels. The fourth power dependence upon radius allows an indicationof the geometric space subject to collateral ventilation regardless ofthe length of the collateral channels.

FIG. 16A illustrates a two-compartment model which is used to generate amethod quantifying the degree of collateral ventilation, including a)determining the resistance to segmental collateral flow R_(coll), b)determining the state of segmental compliance C_(s) and c) determiningthe degree of segmental hyperinflation q_(s). Again, C_(s) characterizesthe compliance of the target compartment or segment. C_(L) representsthe compliance of the rest of the lobe. R_(coll) describes theresistance to the collateral airflow. FIG. 16B provides an electricalcircuit analog model. In this example, at time t=t₁, approximately 5-10ml of 100% inert gas such as He (q_(he)) is infused. After a period oftime, such as one minute, the pressure (P_(s)) & the fraction of He(F_(he) _(s) ) are measured.

The dynamic behavior of the system depicted in FIGS. 16A-16B can bedescribed by the time constant t_(coll)

$\begin{matrix}{\mspace{79mu} {{\text{?} = {R{\text{?} \cdot \underset{\underset{\text{?}}{}}{\frac{C_{S}C_{L}}{C_{S} + C_{L}}}}}}{\text{?}\text{indicates text missing or illegible when filed}}}} & (15)\end{matrix}$

At time t₁=30 s, a known fixed amount of inert gas (q_(he): 5-10 ml of100% He) is rapidly injected into the target compartment C_(s), whilethe rest of the lobe remains occluded; and the pressure (P_(s)) and thefraction of He (F_(he) _(s) ) are measured in the target segment forapproximately one minute (T=60 s). FIGS. 16C-16E illustrate theresulting time changes in volumes, pressures and gas concentrations inthe target compartment C_(s) and the rest of the lobe C_(L). Eqs. 16-21state the mathematical representation of the lung volumes, pressures andgas concentrations at two discrete points in time, t₁ and t₂.

$\begin{matrix}{\mspace{79mu} {{q_{s}\left( t_{1} \right)} = {{q_{s}(0)} + q_{he}}}} & (16) \\{\mspace{79mu} {{{q_{s}\left( t_{2} \right)} + {q_{L}\left( t_{2} \right)}} = {{q_{s}(0)} + {q_{L}(0)} + q_{he}}}} & (17) \\{\mspace{79mu} {{P_{s}\left( t_{1} \right)} = \frac{q_{he}}{C_{s}}}} & (18) \\{\mspace{79mu} {{P_{s}\left( t_{2} \right)} = \frac{q_{he}}{\left( {C_{s} + C_{L}} \right)}}} & (19) \\{\mspace{79mu} {{F\text{?}\left( t_{1} \right)} = \frac{q_{he}}{q_{s}\left( t_{1} \right)}}} & (20) \\{\mspace{79mu} {{{F\text{?}\left( t_{2} \right)} = \frac{q_{he}}{{q\text{?}\left( t_{1} \right)} + {q_{L}\left( t_{2} \right)}}}{\text{?}\text{indicates text missing or illegible when filed}}}} & (21)\end{matrix}$

As a result, the following methods may be performed for each compartmentor segment independently: 1) Assess the degree of segmentalhyperinflation, 2) Determine the state of segmental compliance, 3)Evaluate the extent of segmental collateral communications.

Segmental Hyperinflation

The degree of hyperinflation in the target segment, qs(0), can bedetermined by solving Eq. 16 for qs(0) and subsequently substitutingqs(t₁) from Eq. 20 into Eq. 16 after appropriate solution of Eq. 20 forqs(t₁) as

$\begin{matrix}{{q_{S}(0)} = {q_{he} \cdot \left( \frac{1 - {F_{{he}_{s}}\left( t_{1} \right)}}{F_{{he}_{s}}\left( t_{1} \right)} \right)}} & (22)\end{matrix}$

Segmental Compliance

The state of compliance in the target segment, C_(s), can be determinedsimply by solving Eq. 18 for C_(s) as

$\begin{matrix}{C_{S} = \frac{q_{he}}{P_{S}\left( t_{1} \right)}} & (23)\end{matrix}$

Segmental Collateral Resistance

A direct method for the quantitative determination of collateral systemresistance in lungs, has been described above. Whereas, the calculationbelow offers an indirect way of determining segmental collateralresistance.

The compliance of the rest of the lobe, C_(L), can be determined bysolving Eq. 19 for C_(L) and subsequently substituting C_(s) with Eq.23. Accordingly

$\begin{matrix}{C_{L} = {q_{he} \cdot \frac{{P_{S}\left( t_{1} \right)} - {P_{S}\left( t_{2} \right)}}{{P_{S}\left( t_{1} \right)}{P_{S}\left( t_{2} \right)}}}} & (24)\end{matrix}$

As a result, the resistance to collateral flow/ventilation canalternatively be found by solving Eq. 15 for R_(coll) and subsequentsubstitution into Eq. 15 of C_(s) from Eq. 24 and C_(L) from Eq. 25 as

$\begin{matrix}{R_{coll} = \frac{\tau_{coll}}{C_{eff}}} & (25)\end{matrix}$

where C_(eff) is the effective compliance as defined in Eq. 15.

Additional Useful Calculation for Check and Balances of All Volumes

The degree of hyperinflation in the rest of the lobe, hence q_(L)(0),can be determined by solving Eq. 17 for q_(L)(0) and subsequentlysubstituting qs(t₂)+q_(L)(t₂) from Eq. 21 into Eq. 17 after appropriatesolution of Eq. 21 for qs(t₂)+q_(L)(t₂). Thus

$\begin{matrix}{{q_{L}(0)} = {q_{he} \cdot \left( \frac{{F_{{he}_{s}}\left( t_{1} \right)} - {F_{{he}_{s}}\left( t_{2} \right)}}{{F_{{he}_{s}}\left( t_{1} \right)}{F_{{he}_{s}}\left( t_{2} \right)}} \right)}} & (26)\end{matrix}$

Equation 26 provides an additional measurement for check and balances ofall volumes at the end of the clinical procedure.

1. (canceled)
 2. A method for detecting collateral ventilation into alung compartment in a patient, said system comprising: sealing a distalend of a catheter in an airway feeding the lung compartment by using anoccluding member that is adapted to be expanded in an airway which feedsthe lung compartment such that access to the compartment is providedonly through a passage of the catheter when the occluding member isexpanded; blocking air from entering the lung compartment through thecatheter passage while the patient is inhaling by using a one-way flowelement adapted to be disposed within or in-line with the passage of thecatheter so that flow in a distal-to-proximal direction is allowed andflow in a proximal-to-distal direction is inhibited or prevented;measuring air flow or accumulation from the catheter over time using aflow-measurement device connectable to the catheter; and detectingcollateral ventilation based on the measured air flow or accumulationfrom the catheter over time.
 3. A method as in claim 2, wherein theflow-measurement device comprises a slack collection bag.
 4. A methodfor evaluating a lung compartment comprising: sealing a distal end of acatheter in an airway feeding the lung compartment by using an occludingmember that is adapted to be expanded in an airway which feeds the lungcompartment such that access to the compartment is provided only througha passage of the catheter when the occluding member is expanded;blocking air from entering the lung compartment through the catheterpassage while the patient is inhaling by using a one-way flow elementadapted to be disposed within or in-line with the passage of thecatheter so that flow in a distal-to-proximal direction is allowed andflow in a proximal-to-distal direction is inhibited or prevented;measuring pressure within the lung compartment; and detecting collateralventilation based upon the measured pressure.
 5. The method as in claim4, wherein detecting collateral ventilation comprises calculating adegree of hyperinflation of the target lung compartment.
 6. The methodas in claim 4, wherein detecting collateral ventilation comprisescalculating a state of compliance of the target lung compartment.
 7. Themethod as in claim 4, wherein detecting collateral ventilation comprisescalculating collateral resistance of the target lung compartment.
 8. Themethod as in claim 4, wherein a plurality of measurements of pressureare generated over a predetermined time period.
 9. The method as inclaim 4, further comprising injecting a compound into the lungcompartment to block collateral flow channels.